The MexAB–OprM drug efflux pump is central to multidrug resistance of Pseudomonas aeruginosa. The ability of the tripartite protein to confer drug resistance on the pathogen is crucially dependent on the presence of all three proteins of the complex. However, the role of each protein in the formation of the intact functional complex is not well understood. One of the key questions relates to the (in)ability of MexB to act independently of its cognitive partners, MexA and OprM. In the present study, we have demonstrated that, in the absence of MexA and OprM, MexB can: (i) recruit AcrA and TolC from Escherichia coli to form a functional drug-efflux complex; (ii) transport the toxic compound ethidium bromide in a Gram-positive organism where the periplasmic space and outer membrane are absent; and (iii) catalyse transmembrane chemical proton gradient (ΔpH)-dependent drug transport when purified and reconstituted into proteoliposomes. Our results represent the first evidence of drug transport by an isolated RND (resistance–nodulation–cell division)-type multidrug transporter, and provide a basis for further studies into the energetics of RND-type transporters and their assembly into multiprotein complexes.
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Research Article|
August 13 2010
Promiscuous partnering and independent activity of MexB, the multidrug transporter protein from Pseudomonas aeruginosa
Alexander Welch;
Alexander Welch
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Chidiebere U. Awah;
Chidiebere U. Awah
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Shiheng Jing;
Shiheng Jing
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Hendrik W. van Veen;
Hendrik W. van Veen
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Henrietta Venter
Henrietta Venter
1
1Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
1To whom correspondence should be addressed (email hv214@cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
December 07 2009
Revision Received:
June 23 2010
Accepted:
June 28 2010
Accepted Manuscript online:
June 28 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 430 (2): 355–364.
Article history
Received:
December 07 2009
Revision Received:
June 23 2010
Accepted:
June 28 2010
Accepted Manuscript online:
June 28 2010
Citation
Alexander Welch, Chidiebere U. Awah, Shiheng Jing, Hendrik W. van Veen, Henrietta Venter; Promiscuous partnering and independent activity of MexB, the multidrug transporter protein from Pseudomonas aeruginosa. Biochem J 1 September 2010; 430 (2): 355–364. doi: https://doi.org/10.1042/BJ20091860
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